Abstract：
In the area of drug delivery aided by stimuli-responsive polymers, the biodegradability of nanocarriers is one of the major challenges that needs to be addressed with the utmost sincerity. Herein, a hydrogen sulfide (H2S) responsive hydrophobic dansyl-based trigger molecule is custom designed and successfully incorporated into the water-soluble polyurethane backbone, which is made of esterase enzyme susceptible urethane bonds. The amphiphilic polyurethanes, PUx (x = 2 and 3) with a biotin chain end, formed self-assembled nanoaggregates. A hemolysis and cytotoxicity profile of doxorubicin (DOX)-loaded biotinylated PU3 nanocarriers revealed that it is nonhemolytic and has excellent selectivity toward HeLa cells (biotin receptor-positive cell lines) causing ∼60% cell death while maintaining almost 100% cell viability for HEK 293T cells (biotin receptor-negative cell lines). Furthermore, better cellular internalization of DOX-loaded fluorescent nanocarriers in HeLa cells than in HEK 293T cells confirmed receptor-mediated endocytosis. Thus, this work ensures that the synthesized polymers serve as biodegradable nanocarriers for anticancer therapeutics.
摘要：
在刺激响应性聚合物辅助的药物递送领域，纳米载体的生物降解性是需要以最大的诚意解决的主要挑战之一。在这里，硫化氢（H2S）响应性丹磺基疏水性触发分子是定制设计的，并成功地掺入到水溶性聚氨酯主链中，它是由酯酶酶敏感的氨基甲酸酯键。两亲性聚氨酯，PUx（x=2和3）与生物素链端，形成自组装纳米聚集体。负载多柔比星（DOX）的生物素化PU3纳米载体的溶血和细胞毒性谱显示，它是非溶血的，并且对HeLa细胞（生物素受体阳性细胞系）具有优异的选择性，导致约60％的细胞死亡，同时保持几乎100％的细胞活力HEK293T细胞（生物素受体阴性细胞系）。此外，与HEK293T细胞相比，HeLa细胞中负载DOX的荧光纳米载体的细胞内化更好，证实了受体介导的内吞作用。因此，这项工作确保合成的聚合物作为生物可降解纳米载体的抗癌治疗。
